Trehalose-Modified Silver Nanoparticles as Antibacterial Agents with Reduced Cytotoxicity and Enhanced Uptake by Mycobacteria.

Silver nanoparticles (AgNPs) are potent antimicrobial agents, but their utility is limited due to their relatively high cytotoxicity. In this work, we used trehalose as the ligand to reduce the cytotoxicity of AgNPs without affecting their antimicrobial activities. Trehalose is a disaccharide that is unique to mycobacteria. We showed that trehalose-functionalized AgNPs, AgNP-Tre, drastically increased the viability of A549 cells, especially at high concentrations, for example, from 4% for AgNPs to 67% for AgNP-Tre at 64 μg/mL. The trehalose ligand slowed down the release of silver, and the amount of silver released from AgNP-Tre was less than half of that from AgNPs in the culture medium. Intriguingly, while the maltose (Mal) or tri(ethylene glycol) (TEG) ligand reduced the antibacterial activity of AgNPs against M. smegmatis (minimal inhibitory concentration (MIC) of AgNP-Mal and AgNP-TEG: 4 μg/mL for 7 nm AgNPs), the activity of AgNP-Tre was similar to that of AgNPs (MIC of AgNP-Tre: 1 μg/mL for 7 nm AgNPs). Uptake experiments revealed that the intracellular concentration of AgNP-Tre was 87 and 114% higher than those of AuNP-Mal and AgNP-TEG, respectively. The increased uptake was attributed to the enhanced interactions of AgNP-Tre with mycobacteria promoted by the trehalose ligand.